purpose, function, and proposals for improvement · institutional review board (irb)? •“the irb...

The IRB Purpose, Function, and

Proposals for Improvement

Sara Chandros Hull, PhD Faculty, Department of Bioethics, CC

Director, Bioethics Core, NHGRI

Chair, NHGRI Institutional Review Board

Vice Chair, NIH General Medicine IRB Panel #1 BIOETHICS AT THE NIH

Disclaimers/Disclosures

• No statement in this presentation should

be construed as an official position of the

National Human Genome Research

Institute, National Institutes of Health, or

Department of Health and Human Services.

• The speaker declares no financial conflicts

of interest.

BIOETHICS AT THE NIH

What is an

Institutional Review Board (IRB)?

• “The IRB is an administrative body established to protect the rights and welfare

of human research subjects…” (OPRR 1993)

• Also known as:

– independent ethics committee (IEC)

– ethical review board (ERB)

– research ethics board (REB)


NHGRI Institutional Review Board (circa 2007)


NIH General Medicine IRB Panel #1 (circa 2018)


Roadmap

• Brief history and background of IRBs and

their function

• Composition

• Standards for review

• Proposals for improving IRB functions

• Accreditation

• Centralized IRB review


Why Were IRBs Created?

• Response to scandal

and tragedy

– US: PHS Tuskegee

Study of Untreated

Syphilis in the Negro

Male

• 1932-1972


History of IRBs in the U.S.

• 1974 DHEW National Research Act – National Commission for the Protection

of Human Subjects of Biomedical and Behavioral Research

– Belmont Report (1978)

• 1981 45 CFR 46

– codified IRBs and informed consent


History of IRBs in the U.S.

• 1991 “Common Rule” • Parallel FDA regs:

21 CFR 56

• 2017 Revised Common Rule

– Implementation delayed until 2019


Ethical Requirements:

Independent Review

• Review of research (design,

population, risk/benefit) by

unaffiliated individuals to:

– Minimize impact of potential researcher COI

– Assure public/social accountability

Emanuel et al (2000) JAMA


IRBs at a Glance

• >4000 IRBs in the United States

– And 100s more in 113 countries

Bartlett (2008) JEHRE

• Approx. between 14-40 members

• Meet 1-2x/month weekly!

• Staffed by full time administrators

– Credentialing/professionalization

• Chair ~ 20% (at NIH: 15-100%)


IRB Membership

45 CFR 46.107/21 CFR 56.107

• At least 5 members with varying

backgrounds

• Qualified, diverse, not all men or all

women or same profession

• One scientist, one non-scientist

• One unaffiliated member

• No conflicts

• Special areas of expertise


NIH Membership Requirements

• Non-affiliated members At

majority • Member representing participant

of IRB perspective meetings

• Bioethicist

• Statistician or epidemiologist

• Pharmacist or pharmacologist


Non-Scientist

• “A member whose education, training, background, and occupation would incline

him/her to view research activities from a

standpoint other than any biomedical or

behavioral scientific discipline” (SOP 2)

– “…to fully appreciate risks associated with the

study without being blinded by the lure of

scientific advancement.” (Allison et al 2008)


Roles of Non-Scientists (n=25)

Agree Disagree

• Layperson 68% 32%

• Public representative 28% 72%

• Community Representative 16% 84%

• Research subject advocate* 16% 84%

• vs. non-NIH studies: majority of NS members describe themselves as representing or giving a voice to human subjects

Allison, Abbott, Wichman (2008) IRB


Roles of Non-Scientists non-scientists (n=25); scientists (n=84)

• Main role: review and make

recommendations about informed

consent document (72%; 47%)

• Represent community values, views and

norms (60%; 81%)

• To make conduct of research

accountable to public (88%; 93%)

Allison, Abbott, Wichman (2008) IRB


IRB Functions and Operations

• Reviews:

– Initial protocols

– Continuing review

– Amendments

– Unanticipated problems, non-compliance

– Protocol deviations

– Closures


NIH IRB Review Standards (Belmont-Based)

1. Proposed research design sound/will not

unnecessarily expose subjects to risk

2. Risks reasonable in relation to benefits

and knowledge to be gained

3. Risks to subjects minimized

• Data monitoring plan

4. Equitable subject selection


NIH IRB Review Standards

5. Additional safeguards for vulnerable

participants

6. Informed consent

• Obtained (or waived)

• Documented

• Assent

7. Privacy/confidentiality protections


Additional Considerations

• That investigators and research staff are

qualified (e.g., training, experience)

• Use of ionizing radiation

• Collaborative research – need for other

reviews

• FDA-regulated research

• Duration of approval

– Annual or more often?


IRB Actions

• Simple majority (> half):

– Unconditional approval

– Approval w/stipulations

– Deferred

– Tabled

– Disapproval

• Detailed minutes


Expedited Review

• When no more than minimal risk and

involves certain categories of procedures

(see OHRP guidance)

– To be updated every 8 years


Summary of Key Common Rule

Changes (per OHRP)

• “Promoting individual autonomy” – Changing requirements of informed consent

– Adding broad consent option for secondary research

• “Reducing administrative burden, streamlining IRB

processes” – Removing activities from the definition of research

– Expanding exempt research

– Updating and simplifying expedited review

– Eliminating certain continuing reviews

– Using single IRB review


Q: Does IRB Review Work?

A: We don’t really know – No controlled trials

– No underlying theory or framework of quality

or effectiveness

– Lack of longitudinal assessment

– Little research with key stakeholders beyond

boards/researchers

Nicholls et al (July 30, 2015) PLOS ONE

review of 198 empirical studies


Transformative Effects of IRBs

• “Unquestionably, their very existence has tempered the inevitable propensity of

researchers to pursue investigations without

dispassionately weighing the risks they are

asking others to assume or fully informing

their subjects of them.”

Edgar and Rothman (1995) Milbank Q


Transformative Effects of IRBs


https://thomashunter.name/batman/

https://thomashunter.name/batman

Problems with the Current System

1. Structural problems • Repetitive IRB reviews, inconsistencies in regulations,

absence of resources

2. Procedural problems • Time consuming, inadequate guidance, overly

focused on consent forms

3. Performance assessment problems • Absence of data

Emanuel et al. (2004) Ann Int Med


Proposals to Fix IRBs

• Accreditation

• Centralized IRB review convergence

• Legislative proposals

• Research and innovation


Proposals to Fix IRBs

• Accreditation

• Centralized IRB review

• Legislative proposals

• Research and innovation


AAHRPP Accreditation (n=227)

• Goals:

– Improve systems that protect the rights and welfare of research participants

– Public communication

• Documentation and process focused

• NIH IRP Accreditation (March 18, 2014)

– 3-year renewal (5 thereafter)

– 42 SOPs

• http://ohsr.od.nih.gov/OHSR/pnppublic.php


http://ohsr.od.nih.gov/OHSR/pnppublic.php

Problem: Repetitive IRB Review

• Multisite research is reviewed at each

engaged institution, dissipating limited

resources. Does it… – Foster local efforts to uphold ethical standards

for research?

– Capitalize on IRB’s knowledge of local research

environment and community standards?

Emanuel et al. (2004) Ann Int Med


Proposed Solution: Central IRBs

• Simple definition:

– A single IRB of record for a multicenter clinical trial.

• Detailed definition:

– A properly constituted IRB to which sites cede all [sic] regulatory responsibility for scientific oversight and integrity of the protocol from initial review to termination of the research, including review of informed consent.

Flynn et al. (2013) PLOS ONE


Examples

• NCI Central IRB

• Department of Veterans Affairs

• NeuroNEXT

• NHGRI/Undiagnosed Diseases Network

• PHERRB

– http://ohsr.od.nih.gov/ohsr/public/PHERRB_SO

P28_v1_08-06-15_508.pdf


http://ohsr.od.nih.gov/ohsr/public/PHERRB_SOP28_v1_08-06-15_508.pdf

Central IRB Mechanism

Reliance agreements (SOP 20A)

– “An agreement between NIH and one or more

institutions involved in the same cooperative

research (see definition, below) that assigns

regulatory responsibilities to a specific IRB.”

– Negotiated and executed by OHSRP (at NIH)


Final Common Rule - sIRB

“Creates a requirement for US-based institutions

engaged in cooperative research to use a single

IRB for that portion of the research that takes

place within the United States, with certain

exceptions. This requirement becomes effective 3

years after publication of the final rule.”

https://www.federalregister.gov/documents/2017/01/19/2

017-01058/federal-policy-for-the-protection-of-human-

subjects


https://www.federalregister.gov/documents/2017/01/19/2017-01058/federal-policy-for-the-protection-of-human-subjects

NIH Policy - sIRB

…to establish the expectation that a

single IRB (sIRB) of record will be

used in the ethical review of non-

exempt human subjects research

protocols funded by the NIH that are

carried out at more than one site in

the United States.

Effective date: January 25, 2018


NIH Policy - sIRB

Rationale:

• No evidence that multiple IRB reviews enhance protections for human subjects

• Use of single IRBs may lead to enhanced protections for research participants by:

– eliminating the problem of distributed accountability

– minimizing institutional conflicts of interest

– refocusing IRB time and resources toward review of other studies


Lack of Enthusiasm for CIRBs

• Stakeholder concerns:

– Institutional liability

– Loss of community representation

– Loss of knowledge of local subjects and investigators

– Quality of CIRB review

– Loss of revenue from IRB fees

– Feasibility of working with multiple outside IRBs Loh and Meyer (2004) Acad Med

Klitzman (2011) BMC Med Ethics

Flynn et al. (2013) PLOS ONE


IRB vs. Relying Institution

• IRB

– Training of IRB personnel

– Ensure ethical standards and regs

– Approval of consent forms

– Provide copies of IRB decisions, rosters, minutes

• Relying Institution

– Maintain FWA Credentialing training of staff

– COI review Investigator compliance

– UP and AE reporting HIPAA/Privacy Review

SOP 20A, Flynn et al. (2013) PLOS ONE


http://www.genome.gov/27550959


http://www.genome.gov/27550959

UDN Protocol

• 18 Reliance Agreements

– Coordinating Center

– Clinical enrollment sites

– Cores

• Sequencing

• Model organisms

• Metabolomics

– Biorepository

– Monitor


UDN Consent Forms (n=150!)

• Main study (144)

– 16 consent/assent forms (English + Spanish) x 9

– Plus use of NIH or local short forms

• Patient web pages sub-study (2)

• Site specific (2 x 2)


NIH Policy on Use of a Single IRB for

Multi-Site Research

Exceptions:

– Where review by the proposed sIRB would be

prohibited by a federal, tribal, or state law,

regulation, or policy

– If there is a compelling justification


Exceptions (public comment)

• IHS: “Multi-site studies with central IRB

approval should be required to seek IHS or

Tribal IRB approval, as appropriate, for

research conducted within the jurisdiction of

federally recognized AI/AN Tribes”


Exceptions (public comment)

• Tribal IRBs ensure that research

– is conducted in a community engaged manner

– does not deplete or divert limited tribal

resources away from direct patient care

– findings are first shared with tribal leadership,

tribal communities, and key stakeholders


Revised Common Rule:

Acknowledging Tribal Sovereignty

“Thus, if the official governing body of a tribe

passes a tribal law that provides additional

protections for human subjects, the Common

Rule does not affect or alter the applicability of

such tribal law ...” Federal Policy for the Protection of Human Subjects/Final

Rule 2017, 7158, Executive Summary II.E.2


http://www.primr.org/webinars/sept2016/


http://www.primr.org/webinars/sept2016/

Thank you!


purpose, function, and proposals for improvement · institutional review board (irb)? •“the irb...

Documents